The main objectives of this proposed research are: 1. To perform sequential analysis of azodye-induced carcinogenesis in rat liver in order to trace the causal connection between essential steps in this process. This will be done using the following tools: a) gamma-glutamyl transferase (glutathionase, GT-ase) as a Marker, b) glutathione (GSH) as a natural substrate of GT-ase, c) the inhibitor Disulfiram, and d) the increase in the content of neuraminic acid in the marker. 2. To identify the cells from which the cancerous cell line originates with the help of these tools. 3. To investigate the basic reaction that may underlie the change in physiological, physical and chemical properties of the Marker during hepatocarcinogenesis. 4. To investigate histochemically in a greater detail the role of GT-ase as a marker in several experimental and human cancers of epithelial nature. 5. To define the properties of, and eventually to find, a General Marker for many, perhaps all, forms of cancer. This aim is based on our working hypothesis that all forms of cancer are only various manifestations of the same fundamental disorder in enzyme regulation. This disorder is reflected in the change of Marker's properties. Consequently, various classes of cancer have different markers but all of them have in common the same pattern of change during carcinogenesis resulting in the development of tumors. The methods to be used for reaching these objectives will include: isolation of normal and cancerous GT-ase, measurement of their half-lives during carcinogenesis. Histochemistry of GT-ase. Determination of neuraminic acid. Inhibitors of protein synthesis of transcriptional and translational stage. Changes in patterns of m-RNA stability and total DNA contents. Autoradiography. Strains of 'spontaneous' hepatomas and carcinogenesis induced by a single dose of selected carcinogens.